Interpretive Handbook

Conventional cytogenetic studies can identify the presence of chromosome abnormalities and the presence or absence of most mosaic conditions. Conventional cytogenetic studies utilize a variety of staining techniques to identify each chromosome. With these methods, structural or numeric chromosome abnormalities are detected in approximately 11% of peripheral blood specimens referred to our Cytogenetic Laboratory from patients with congenital disorders.  

In approximately 2% of these chromosomally abnormal cases, the genetic makeup of the chromosome anomaly can be identified, but not completely characterized, by conventional techniques alone. For malignant disorders, the proportion of specimens with unresolvable chromosome abnormalities is much higher. In our experience, the use of FISH with chromosome-specific paint probes (collections of unique DNA sequences for specific chromosomes), locus-specific probes, and alpha-satellite probes can help establish the genetic makeup of a high proportion of chromosome abnormalities. This includes abnormalities that cannot be accurately characterized by conventional methods such as unusual structural alterations, questionable mosaicism of an abnormality, and unbalanced chromosome abnormalities such as deletions, duplications, and translocations that cannot be resolved by studies on other family members. Scoring chromosomal aneuploidy abnormalities by FISH is generally easier than by conventional cytogenetic methods and can be done by use of either interphase or metaphase cells. Thus, large numbers of cells can be scored to more accurately establish the frequency of chromosome abnormalities.

We recommend that conventional chromosome analysis be performed first to establish the constitutional karyotype and determine whether or not the patient has chromosome mosaicism.

As an adjunct to conventional chromosome studies, to resolve unusual or complex structural alterations, questionable mosaicism, and unbalanced chromosome abnormalities that cannot be resolved by studies on other family members

To diagnose certain disorders caused by a deletion or duplication of a given chromosome region

To identify unbalanced structural abnormalities in cases where this information is needed more rapidly than conventional chromosome analysis can supply (eg, situations where genetic counseling is needed quickly to decide treatment, but conventional cytogenetic studies would require studying multiple family members)

To help establish the origin and centromeric make up of dicentric or marker chromosomes

In suboptimal chromosome preparations, FISH can help confirm the results of conventional chromosome analysis

To determine whether a child’s deletion or duplication detected via array comparative genomic hybridization (aCGH) is de novo or inherited

An interpretive report is provided.

Structural alterations involving highly repetitive DNA sequences such as the chromosome 1 p-arm terminal region and pericentromeric regions of most chromosomes may not show bright fluorescence with some of these probes.

It may not always be possible to detect chromosome segments that are smaller than 1.5 megabases. Thus, subtle structural abnormalities may not be detected with this method.

The alpha-satellite probes are not available for every chromosome. Some of the alpha-satellite probes cross-hybridize with other chromosomes (eg, chromosomes 13/21, 14/22, and 1/5/19).

Both chromosome-specific paint probes and alpha-satellite probes work best when the cytogenetic preparations are <4 weeks old.

Normal results do not rule out the possibility of subtle or variant abnormalities.  

Normal results for any FISH study do not rule out abnormalities other than those being specifically targeted.

An interpretive report will be provided.

1. Jalal SM, Law ME, Dewald GW: Atlas of Whole Chromosome Paint Probes. Normal Patterns and Utility for Abnormal Cases. Rochester, MN, Mayo Foundation, 1995

2. Jalal SM, Law ME, Christensen ER, et al: Method for sequential staining of GTL-banded metaphases with fluorescent-labeled chromosome-specific paint probes. Am J Med Genet 1993;46:98-103

3. Kraker WJ, Borell TJ, Schad CR, et al: Fluorescent in situ hybridization: use of whole chromosome paint probes to identify unbalanced chromosome translocations. Mayo Clin Proc 1992;67:658-662

4. Schad CR, Kraker WJ, Jalal SM, et al: Use of fluorescent in situ hybridization for marker chromosome identification in congenital and neoplastic disorders. Am J Clin Pathol 1991;96:203-210